Cartilage is a unique tissue that functions to cushion the impact between bones and is a target for degenerative changes that result in osteoarthritis (OA), a disease afflicting millions of elderly individuals. OA involves changes in expression of matrix proteins such as collagen II as well as death of cells that comprise cartilage, the chondrocytes. We previously identified a region in the collagen II gene that functions as a chondrocyte-specific enhancer of transcription and further determined that a decamer sequence serves as binding site for chondrocyte-specific proteins. Recently, we demonstrated that a known DNA-binding protein (T-160, SSRP) binds to the enhancer region (although not to the decamer motif) and further that transcription factors belonging to the HLH family interact with the decamer sequence. Studies are ongoing to clone the chondrocyte-specific factors that bind to the enhancer. We are also studying the formation and degeneration of cartilage in various model systems. We have shown that factors associated with aged mice will suppress the formation of cartilage both in vivo and in vitro. Finally, we are testing the hypothesis that programmed cell death (apoptosis) may be responsible for the loss of chondrocytes that is observed with aging and OA.